Outline

Cervical cancer has been recognized as a rare outcome of a common sexually transmitted infection. The etiological association is restricted to a limited number of so called “high risk” human papillomavirus types. The association is causal in nature and under optimal testing systems HPV DNA can be identified in all specimens of invasive cervical cancer. However, only the persistent infection with “high risk” human papillomavirus types is a necessary cause of cervical cancer. Cofactors that modify the risk among HPV DNA positive women include the use of oral contraceptives for 5 or more years, smoking, high parity (5 or more full term pregnancies) and previous exposure to other sexually transmitted diseases such as clamydia trachomatis and herpes virus type 2. Women exposed to the human immunodeficiency virus (HIV) are at high risk of HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer. The main oncoproteins of “high risk” HPV types are E6 and E7, which can bind to and degrade cellular tumor suppressor proteins like p53 and pRb. In addition, the E6 protein induces the activity of the telomerase enzyme and impairs the efficiency of the base excision DNA repair pathway. The activity of the E6 and E7 proteins pushes persistently infected cells into the S-phase and leads to the accumulation of chromosomal abnormalities and centrosome duplications. A prophylactic vaccine directed against the two main high risk types (16 and 18) is available 2006. However, successful therapeutic vaccines and specific antiviral therapies have not yet been developed.